CDx in oncology · 9/27/2018 · INSERM U900 Research unit Versailles Saint-Quentin-en-Yvelines...
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CDx in oncology Prof. Christophe Le Tourneau, MD, PhD Institut Curie – Paris & Saint-Cloud – France Head, Department of Drug Development and Innovation (D 3 i) INSERM U900 Research unit Versailles Saint-Quentin-en-Yvelines University FEAM – Geneva – September 27, 2018
Transcript of CDx in oncology · 9/27/2018 · INSERM U900 Research unit Versailles Saint-Quentin-en-Yvelines...
CDx in oncologyProf. Christophe Le Tourneau, MD, PhD
Institut Curie – Paris & Saint-Cloud – France
Head, Department of Drug Development and Innovation (D3i)
INSERM U900 Research unit
Versailles Saint-Quentin-en-Yvelines University
FEAM – Geneva – September 27, 2018
Treatment of cancer
Primary tumor Metastases
Treatment of cancer
→ Aim = cure
Treatment of cancer
→ Aim = cure
Surgery
Radio-
therapy
Drugs For a limited time
Local treatments
Treatment of cancer
Treatment of cancer
Drugs
Surgery
Radio-
therapy
Curable situation in ~5% of cases (exception of germline tumors [95%])
Chronic disease
Treatment for life
Treatment of cancer
20th century 21st century
Surgery
Radiotherapy
Chemotherapy
Treatment of cancer
20th century 21st century
Surgery
Radiotherapy
Chemotherapy
Targeted therapy
Treatment of cancer
Targeted therapies Tumor type Biomarker
EGFR tyrosine kinase inhibitors Lung EGFR mutations
HER2-targeting agents Breast
Gastric
HER2 amplifications
HER2 amplifications
EGFR monoclonal antibodies Colorectal KRAS mutations
BRAF inhibitors Melanoma BRAF mutations
ALK inhibitors Lung ALK translocations
ROS1 inhibitors Lung ROS1 translocations
KIT inhibitors GIST KIT expression
Treatment of cancer
Targeted therapies Tumor type Biomarker Survival benefit
EGFR tyrosine kinase inhibitors Lung EGFR mutations Years
HER2-targeting agents Breast
Gastric
HER2 amplifications
HER2 amplifications
Years
Months
EGFR monoclonal antibodies Colorectal KRAS mutations Months
BRAF inhibitors Melanoma BRAF mutations Months
ALK inhibitors Lung ALK translocations Years
ROS1 inhibitors Lung ROS1 translocations Years
KIT inhibitors GIST KIT expression Years
Treatment of cancer
Targeted therapies Tumor type Biomarker Survival benefit
EGFR tyrosine kinase inhibitors Lung EGFR mutations Years
HER2-targeting agents Breast
Gastric
HER2 amplifications
HER2 amplifications
Years
Months
EGFR monoclonal antibodies Colorectal KRAS mutations Months
BRAF inhibitors Melanoma BRAF mutations Months
ALK inhibitors Lung ALK translocations Years
ROS1 inhibitors Lung ROS1 translocations Years
KIT inhibitors GIST KIT expression Years
Hormone therapy Breast ER/PR expression Years
Treatment of cancer
Targeted therapies Tumor type Biomarker Survival benefit
EGFR tyrosine kinase inhibitors Lung EGFR mutations Years
HER2-targeting agents Breast
Gastric
HER2 amplifications
HER2 amplifications
Years
Months
EGFR monoclonal antibodies Colorectal KRAS mutations Months
BRAF inhibitors Melanoma BRAF mutations Months
ALK inhibitors Lung ALK translocations Years
ROS1 inhibitors Lung ROS1 translocations Years
KIT inhibitors GIST KIT expression Years
Hormone therapy Breast ER/PR expression Years
NTRK inhibitors All NTRK translocations Years
Treatment of cancer
Targeted therapies Tumor type Biomarker Survival benefit
EGFR tyrosine kinase inhibitors Lung EGFR mutations Years
HER2-targeting agents Breast
Gastric
HER2 amplifications
HER2 amplifications
Years
Months
EGFR monoclonal antibodies Colorectal KRAS mutations Months
BRAF inhibitors Melanoma BRAF mutations Months
ALK inhibitors Lung ALK translocations Years
ROS1 inhibitors Lung ROS1 translocations Years
KIT inhibitors GIST KIT expression Years
Hormone therapy Breast ER/PR expression Years
NTRK inhibitors All NTRK translocations Years
mTOR inhibitors Breast/Kidney/Endocrine - Months
VEGF(R) inhibitors Lung/Breast/Colorectal/
Glioblastoma/Kidney/
Ovarian/Gastric
- Months
CDK4/6 inhibitors Breast - Months
Treatment of cancer
HER-2
20%
Trastuzumab
(Herceptin®)
Amplification
Lapatinib
(Tykerb®)
Treatment of cancer
HER2+ breast cancer
Trastuzumab
(Herceptin®)
→ Risk of recurrence
decreased by 50%
Treatment of cancer
HER2+ metastasic
breast cancer
Trastuzumab
(Herceptin®)
→ Median overall
survival increased from
<2 to >6 years
Treatment of cancer
20th century 21st century
Surgery
Radiotherapy
Chemotherapy
Targeted therapy
Immunotherapy
Treatment of cancer
Tumor type Setting Biomarker
Lung 1st line single agent
1st line + chemo
2nd line single agent
Adjuvant post CRT
PD-L1 expression
-
-
-
Head and Neck 2nd line single agent -
Bladder 2nd line single agent -
Kidney 1st line single agent -
Melanoma Any line single agent -
Lymphoma 2nd line single agent -
Merckel cell 2nd line single agent -
Treatment of cancer
Tumor type Setting Biomarker % responders Survival benefit
Lung 1st line single agent
1st line + chemo
2nd line single agent
Adjuvant post CRT
PD-L1 expression
-
-
-
50%
NA
20%
NA
Months
Months
Months
Months
Head and Neck 2nd line single agent - 20% Months
Bladder 2nd line single agent - 20% Months
Kidney 1st line single agent - 20% Months
Melanoma Any line single agent - 40% Months
Lymphoma 2nd line single agent - 80% Months
Merckel cell 2nd line single agent - 30% Months
Treatment of cancer
Treatment of cancer
Tumor type Setting Biomarker % responders Survival benefit
Lung 1st line single agent
1st line + chemo
2nd line single agent
Adjuvant post CRT
PD-L1 expression
-
-
-
50%
NA
20%
NA
Months
Months
Months
Months
Head and Neck 2nd line single agent - 20% Months
Bladder 2nd line single agent - 20% Months
Kidney 1st line single agent - 20% Months
Melanoma Any line single agent - 40% Months
Lymphoma 2nd line single agent - 80% Months
Merckel cell 2nd line single agent - 30% Months
All Any line single agent MSI 40% Years
Challenges
1) Identification of resistance biomarkers to
targeted therapies/immunotherapy
Challenges
1) Identification of resistance biomarkers to
targeted therapies/immunotherapy- T790M EGFR mutation in EGFR-mutated lung cancer
patients treated with EGFR inhibitors
- ESR1 mutations in breast cancer patients treated with
aromatase inhibitors
Challenges
1) Identification of resistance biomarkers to
targeted therapies/immunotherapy- T790M EGFR mutation in EGFR-mutated lung cancer
patients treated with EGFR inhibitors
- ESR1 mutations in breast cancer patients treated with
aromatase inhibitors
→Sequential analyses of tumor DNA
Challenges
1) Identification of resistance biomarkers to
targeted therapies/immunotherapy- T790M EGFR mutation in EGFR-mutated lung cancer
patients treated with EGFR inhibitors
- ESR1 mutations in breast cancer patients treated with
aromatase inhibitors
→Sequential analyses of tumor DNA
→ctDNA analysis might be a solution to avoid tumor
biopsies
Challenges
2) Identification of biomarkers of efficacy of
immunotherapy
Challenges
2) Identification of biomarkers of efficacy of
immunotherapy- a minority of cancer patients benefit from
immunotherapy although survival benefits are reported
without using biomarkers
Challenges
Ferris et al. NEJM 2016;375:1856-67
Challenges
2) Identification of biomarkers of efficacy of
immunotherapy- a minority of cancer patients benefit from
immunotherapy although survival benefits are reported
without using biomarkers
→ Need for identifying biomarkers to avoid ineffective
treatments to patients and to preserve the financial health
of our systems
Challenges
3) Democratization of high throughput
technologies to identify targets
Challenges
3) Democratization of high throughput
technologies to identify targets- analysing multiple biomarkers in a single assay is a gain
of time, tissue and likely money
Challenges
3) Democratization of high throughput
technologies to identify targets- analysing multiple biomarkers in a single assay is a gain
of time, tissue and likely money
→Concordance between the results of a single gene CDx
and NGS?
Challenges
3) Democratization of high throughput
technologies to identify targets- analysing multiple biomarkers in a single assay is a gain
of time, tissue and likely money
→Concordance between the results of a single gene CDx
and NGS?
→How CDx companies get their money back?
Conclusions
• The development of biomarkers has
emerged with the advent of targeted
therapies leading to impressive efficacy in
enriched patient populations
Conclusions
• The development of biomarkers has
emerged with the advent of targeted
therapies leading to impressive efficacy in
enriched patient populations
• The development of biomarkers for
immunotherapy is key since only a minority
of patients benefit from these drugs
Conclusions
• The democratization of NGS is a gain of
time, tissue, and likely money. However, the
quality of the data has to be ensured and the
impact on CDx companies be discussed.
